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Biomedical subjects

L R Weintraub

Publications and source records attributed to L R Weintraub.

At least 19 recordsLinked to original sources

Collection of mobilized blood progenitor cells for hematopoietic rescue by large-volume leukapheresis.

BACKGROUND: Mobilized blood progenitor cells rapidly reconstitute hematopoiesis in patients after dose-intensive chemotherapy. However, optimal timing and methods of mobilized blood progenitor cell collection have yet to be fully defined. STUDY DESIGN AND METHODS: The utility of large-volume leukapheresis (LVL; > 15 L blood processed) in collecting target doses of mononuclear cells (7 x 10(8)/kg) for use in autologous hematopoietic rescue was investigated. LVL was begun at a standardized interval (14 days) after a course of limited chemotherapy and subsequent daily recombinant human granulocyte-macrophage-colony-stimulating factor administration to mobilize blood progenitor cells into the circulation. With each LVL procedure, mononuclear cells, colony-forming units-granulocyte-macrophage (CFU-GM), burst-forming units-erythroid, mixed colonies, total clonogenic progenitor cells, and CD34+ cells collected per kg of patient weight were counted. After high-dose chemotherapy and infusion of cryopreserved mobilized blood progenitor cells, the days needed for neutrophils to reach levels of > 0.5 x 10(9) per L and for platelets to reach levels of > 20 x 10(9) per L were recorded. RESULTS: In 14 previously treated cancer patients, an average of 28.9 +/- 4.9 L of blood was processed per LVL (n = 35) to collect medians of 2.5 x 10(8) mononuclear cells per kg (range, 1.0-7.4), 14 x 10(4) CFU-GM per kg (0-208), 27 x 10(4) clonogenic progenitor cells per kg (0-370), and 2.8 x 10(6) CD34+ cells per kg (0-112.5). Fifty-seven percent of patients (8/14) required one or two LVL procedures to collect adequate blood progenitor cells (range, 1-4). After dose-intensive chemotherapy, 13 patients received medians of 6.8 x 10(8) mononuclear cells per kg (range, 5.1-9.9), 53 x 10(4) CFU-GM per kg (9-208), and 12 x 10(6) CD34+ cells per kg (3.6-112.5). Rapid hematopoietic reconstitution occurred with 10 days (range, 8-12) and 9 days (6-15), respectively, for neutrophil and platelet recoveries. CONCLUSION: Scheduled LVL, beginning on Day 14 after the administration of granulocyte-macrophage-colony-stimulating factor following chemotherapy, is a convenient and efficient method of collecting blood progenitor cells. The mononuclear cells so obtained effected consistent and rapid hematopoietic reconstitution in a highly reproducible manner in a group of heavily treated patients.

Adult

Synchronization of plasma exchange and cyclophosphamide in severe and refractory autoimmune hemolytic anemia.

Two cases of severe autoimmune hemolytic anemia (AIHA) that failed multiple treatment modalities obtained complete and long-lasting remissions with a combination of three one volume plasma exchange (PE) on succeeding days followed 6 hours later on the 3rd day by cyclophosphamide (cyc) 750 mg/m2 IV, and cyc/prednisone (pred) qd tapering to either no therapy or minimal therapy over a 6 month period. Both cases remain without evidence of AIHA after 43 and 19 months follow-up. Possible non-exclusive mechanisms that explain this favorable outcome are enhanced cytotoxic effect of cyc on proliferating lymphocytes participating in the antibody rebound phenomena, suppression of B lymphocytes with daily cyc/pred, and/or formation of anti-idiotype antibodies.

Anemia, Hemolytic, Autoimmune

Reversal of bone marrow fibrosis and subsequent development of polycythemia in patients with myeloproliferative disorders.

Bone marrow fibrosis is a characteristic finding in agnogenic myeloid metaplasia and in the spent phase of polycythemia vera. It is commonly believed that the reticulin deposition is irreversible. However, we report four patients who demonstrated clinical and laboratory evidence of transition from myelofibrosis to polycythemia. The transition was documented by improvement in the hemoglobin concentration and by determination of the Cr51 red blood cell mass, accompanied by a resolution of the fibrosis on serial bone marrow biopsies. Two of the patients had been treated with alkylating agents and splenectomy, one with myelosuppressive therapy without splenectomy, and one with splenectomy alone. These findings indicate that bone marrow fibrosis in the chronic myeloproliferative disorders is not always an irreversible phenomenon. Pathogenetic implications will be discussed.

Aged

Late postsplenectomy recurrence of thrombotic thrombocytopenic purpura responding to removal of accessory spleen.

The present report describes a patient who experienced recurrence of thrombotic thrombocytopenic purpura 10 years after the initial episode. The patient had been successfully treated with steroids and splenectomy and had complete clinical and hematologic remission. Thrombotic thrombocytopenic purpura recurred 10 years later and did not respond to steroids and plasmapheresis. The presence of an accessory spleen was demonstrated by technetium scanning. Surgical removal of the accessory spleen resulted again in prompt and complete recovery.

Adult

Pathogenesis of hepatic fibrosis in experimental iron overload.

Significant increases in prolyl hydroxylase activity, a key enzyme in the collagen biosynthetic pathway, were noted in the hepatic homogenates of iron-loaded animals as compared to controls. The increase in prolyl hydroxylase activity was seen without any light microscopic histologic evidence of cell necrosis or accumulation of collagen in the livers from the iron-loaded animals. However, utilizing electron microscopy, collagen fibrils were demonstrated immediately adjacent to the hepatocytes in the iron-loaded animals but not the controls. No fibroblasts or inflammatory cells were noted in this area. There was no evidence of damage to the subcellular organelles of the iron-loaded hepatocytes. The hydroxyproline content of the iron-loaded livers was also shown to be increased. These experimental studies in conjunction with clinical observations described below suggest that in vivo iron overload may have a primary effect on stimulating collagen synthesis by hepatocytes.

Animals

Quantification of P-32 removed during leukapheresis by bremsstrahlung counting.

The activity of P-32 removed during leukapheresis of a patient previously administered P-32 for therapy of chronic myelogenous leukemia (CML) was determined. The bremsstrahlung produced by P-32 beta rays in the pheresis bags allowed the quantitation of radioactivity by well counting in a sodium iodide detector and by a gamma camera. Bremsstrahlung counting demonstrated that leukapheresis removes such a small amount of radioactivity that the therapeutic effect of a previously administered P-32 dose was still valid. Bremsstrahlung counting offers advantages to a Nuclear Medicine Department over the conventional use of a liquid scintillation counter to detect P-32 beta rays in that it is simpler and more readily available.

Humans

Leukocyte larceny: a cause of spurious hypoxemia.

Multiple blood specimens with different leukocyte counts from two patients with extreme leukocytosis secondary to leukemia and unexplained hypoxemia were tonometered with a gas of known oxygen concentration and the decay of oxygen tension (PO2) was measured over time. The decay in PO2 in the first 2 minutes for blood with leukocyte counts of between 55.2 X 10(3)/mm3 and 490.0 X 10(3)/mm3 ranged from 13 to 72 torr. The degree of PO2 decay was blunted by placing the blood on ice and was obliterated by adding potassium cyanide. Thus, extreme leukocytosis secondary to leukemia can cause spurious hypoxemia and spurious lowering of the mixed venous PO2 due to oxygen consumption by leukocytes ("leukocyte larceny").

Adult

Leukocytic fibrinolysis in myelomonocytic leukemia.

A case of myelomonocytic leukemia is described in which an increase in primary fibrinolytic activity produced a severe hemorrhagic diathesis. The leukemic cells were demonstrated to be the source of the fibrinolytic activity. Utilizing a fibrin coated slide technique, the intact leukemic cells were shown to release their fibrinolytic activity and to induce local lysis. Intact leukocytes from normal subjects and other patients with acute leukemia of varied cell types were unable to release fibrinolytic activity although in some of the leukemic preparations, increased fibrinolytic activity was demonstrated after in vitro disruption of the cells.

Animals

Effect of iron saturation of transferrin on hepatic iron uptake: an in vitro study.

Studies were performed to delineate the effect of percentage of saturation of transferrin and total iron concentration on the rate of uptake of iron by the perfused rat liver. Normal and iron-deficient rat livers were perfused with sera that contained varying concentrations of 59Fe-labeled iron and transferrin saturation. Varying the percentage of saturation of transferrin while maintaining a constant concentration of iron did not influence the hepatic uptake of iron. However, raising the concentration of iron in the perfusate while maintaining a constant saturation of transferrin did increase the uptake of iron by the liver. At similar concentrations of iron and transferrin saturation, iron-deficient livers took up greater amounts of iron than did normal livers. In our experiments, the hepatic uptake of transferrin-bound iron is determined by (1) the concentration of iron in perfusate and (2) the status of iron stores in the liver being perfused.

Animals

Micropinocytosis of transferrin by developing red cells: an electron-microscopic study utilizing ferritin-conjugated transferrin and ferritin-conjugated antibodies to transferrin.

Electron-microscopic examination of rat reticulocytes and normoblasts incubated with transferrin conjugated to ferritin or ferritin-labeled antitransferrin revealed binding of ferritin conjugates to the surface membrane, and uptake of ferritin conjugates in micropinocytotic vesicles. No binding or endocytosis of ferritin was visualized when rat reticulocytes or normoblasts were incubated with ferritin alone or ferritin conjugated to nonspecific rabbit IgG. These observations support the concept that transferrin binds to a surface membrane receptor and is subsequently internalized by the developing red cell. Time course and temperature dependence studies suggest the endocytosis of transferrin may be an important mechanism in delivery of iron to the developing red cell.

Animals